CircRhoC promotes tumorigenicity and progression in ovarian cancer by functioning as a miR-302e sponge to positively regulate VEGFA.

Ovarian cancer is a leading cause of deaths due to gynaecological malignancy. While endogenous non-coding circular RNAs (circRNAs) in cancer have attracted attention, their roles in ovarian cancer are not known. We used qRT-PCR to quantify expression of circRhoC in ovarian cancer tissues and normal tissues. The effects of overexpressing or destruction of circRhoC on the phenotype of ovarian cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay assesses the microRNA sponge function of circRhoC. Western blotting was used to confirm the effects of circRhoC and microRNA on target gene expression. Our results showed that circRhoC was significantly up-regulated in ovarian cancer tissues compared to normal ovarian tissues. Overexpression of circRhoC in CAOV3 ovarian cancer cell increased cell viability, migration and invasion ability; destroying circRhoC in A2780 had the opposite effects and inhibited ovarian tumour cell A2780 dissemination in the peritoneum in vivo. We confirmed circRhoC functions as a sponge for miR-302e to positively regulate VEGFA; FISH experiments showed that circRhoC could co-focal with miR-302e; besides, overexpression of miR-302e reversed the ability of circRhoC to positively regulate VEGFA, and what's more, RIP assay showed that circRhoC could directly bind with VEGFA; besides, VEGFA expression level in ovarian cancer tissues was positively associated with circRhoC expression. In conclusion, the oncogenic effect of RhoC in ovarian cancer is at least in part due to circRhoC, which functions not only as a miR-302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression.

Wang LL ，Zong ZH ，Liu Y ，Guan X ，Chen S ，Zhao Y ... -  《-》

circEPSTI1 regulates ovarian cancer progression via decoying miR-942.

Increasing studies show that circular RNAs (circRNAs) play vital roles in tumour progression. But, how circRNAs function in ovarian cancer is mostly unclear. Here, we detected the expression of circEPSTI1 in ovarian cancer and explored the function of circEPSTI1 in ovarian cancer via a series of experiments. Then, we performed luciferase assay and RNA immunoprecipitation (RIP) assay to explore the competing endogenous RNA (ceRNA) function of circEPSTI1 in ovarian cancer. qRT-PCR verified that circEPSTI1 was overexpressed in ovarian cancer. Inhibition of circEPSTI1 suppressed ovarian cancer cell proliferation, invasion but promoted cell apoptosis. Luciferase assays and RIP assay showed that circEPSTI1 and EPSTI1 (epithelial stromal interaction 1) could directly bind to miR-942. And circEPSTI1 could regulate EPSTI1 expression via sponging miR-942. In summary, circEPSTI1 regulated EPSTI1 expression and ovarian cancer progression by sponging miR-942. circEPSTI1 could be used as a biomarker and therapeutic target in ovarian cancer.

Xie J ，Wang S ，Li G ，Zhao X ，Jiang F ，Liu J ，Tan W ... -  《-》

CircWHSC1 promotes ovarian cancer progression by regulating MUC1 and hTERT through sponging miR-145 and miR-1182.

Zong ZH ，Du YP ，Guan X ，Chen S ，Zhao Y ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis.

Wu B ，Zhang L ，Yu Y ，Lu T ，Zhang Y ，Zhu W ，Song Q ，Lv C ，Guo J ，Tian Y ，Deng N ... -  《-》

circ-CSPP1 promotes proliferation, invasion and migration of ovarian cancer cells by acting as a miR-1236-3p sponge.

Circular RNAs are known to participate in tumorigenesis through a variety of pathways, and as such, have potential to serve as molecular markers in tumor diagnosis and treatment. Here, using quantitative reverse transcription (qRT)-PCR, we showed that circ-CSPP1 is highly expressed in ovarian cancer (OC) tissues. Particularly, we detected circ-CSPP1 expression in three OC cell lines; of which, OVCAR3 and A2780 demonstrated higher levels of circ-CSPP1 expression, and CAOV3 showed lower circ-CSPP1 expression level. Subsequent silencing of circ-CSPP1 in OVCAR3 and A2780 cell lines revealed decreased cell growth, migration and invasion, while overexpression of circ-CSPP1 caused opposite results We also found that miR-1236-3p is a target of circ-CSPP1. Circ-CSPP1 silencing increased the expression of miR-1236-3p, and circ-CSPP1 overexpression decreased miR-1236-3p expression. MiR-1236-3p reportedly plays a tumor-suppressor role in OC by targeting zinc finger E-box binding homeobox 1 (ZEB1). In agreement with this, we showed that silencing circ-CSPP1 significantly decreased ZEB1 expression at both RNA and protein levels, and epithelial-mesenchymal transition (EMT) related markers (E-cadherin and N-cadherin) varied with ZEB1 expression. Circ-CSPP1 silencing also caused decreased expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor A (VEGFA), both of which are related to tumorigenesis. Overexpression of circ-CSPP1 had opposite effects. In addition, we indicated that the tumor-promoting effect was inhibited after we transfected miR-1236-3p into circ-CSPP1 overexpressing OC cells. Altogether, our findings suggest that by acting as a miR-1236-3p sponge, circ-CSPP1 impairs the inhibitory effect of miR-1236-3p on ZEB1, which subsequently promotes EMT and OC development.

Li QH ，Liu Y ，Chen S ，Zong ZH ，Du YP ，Sheng XJ ，Zhao Y ... -  《-》